Bacterial or yeast vaginitis is a common and noxious problem which at one time or another affects nearly all women. Overgrowth of various microbial species in the vagina has been implicated in prematurity and low birth weight with its attendant complications. The interaction between host defense systems in the vagina and resident or exogenous microbes has not been adequately studied. The vaginal epithelium is covered by a thin layer of fluid that forms a potential barrier to microbial colonization, adherence and invasion. Based on preliminary data, we hypothesize that his fluid contains antimicrobial polypeptides that mediate the resistance of the vaginal epithelium to invasion by microorganisms, defend lesions generated by microtrauma, and regulate the composition of the vaginal microflora by selective toxicity to exogenous species. Genetic or acquired disturbances in the composition of this fluid may result in increased susceptibility to colonization by endogenous or exogenous microbial species. To explore this hypothesis, the following specific aims are proposed: 1. Identify the principal polypeptides of human vaginal secretions. 2. Analyze the antimicrobial spectrum and interactions of the most active components. 3. Characterize the regulation of each component during the menstrual cycle. 4. Search for abnormalities in the polypeptide composition of vaginal fluid in patients with vaginitis/vaginosis. In the aggregate, these specific aims will provide a comprehensive framework for understanding the role of epithelial fluid in innate host defense of the vagina. This project is greatly facilitated by the synergistic expertise and resources of the other projects, especially in the area of the highly complex microbiology of the vagina.